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Emergency and critical care applications for contrast-enhanced ultrasound

Published:April 21, 2018DOI:https://doi.org/10.1016/j.ajem.2018.04.044

      Abstract

      Introduction

      Contrast-enhanced ultrasound (CEUS) using intravascular microbubbles has potential to revolutionize point-of-care ultrasonography by expanding the use of ultrasonography into clinical scenarios previously reserved for computed tomography (CT), magnetic resonance imaging, or angiography.

      Methods

      We performed a literature search and report clinical experience to provide an introduction to CEUS and describe its current applications for point-of-care indications.

      Results

      The uses of CEUS include several applications highly relevant for emergency medicine, such as solid-organ injuries, actively bleeding hematomas, or abdominal aortic aneurysms. Compared with CT as the preeminent advanced imaging modality in the emergency department, CEUS is low cost, radiation sparing, repeatable, and readily available. It does not require sedation, preprocedural laboratory assessment, or transportation to the radiology suite.

      Conclusions

      CEUS is a promising imaging technique for point-of-care applications in pediatric and adult patients and can be applied for patients with allergy to CT contrast medium or with impaired renal function. More high-quality CEUS research focusing on accuracy, patient safety, health care costs, and throughput times is needed to validate its use in emergency and critical care settings.

      Abbreviations:

      CEUS (contrast-enhanced ultrasound), CT (computed tomography), ED (emergency department), FAST (focused assessment with sonography in trauma), FDA (US Food and Drug Administration), ICU (intensive care unit), UCA (ultrasonography contrast agent)

      Keywords

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      References

        • Moore C.L.
        • Copel J.A.
        Point-of-care ultrasonography.
        N Engl J Med. 2011; 364: 749-757
        • Levy J.A.
        • Noble V.E.
        Bedside ultrasound in pediatric emergency medicine.
        Pediatrics. 2008; 121: e1404-1412
        • Evans N.
        • Gournay V.
        • Cabanas F.
        • et al.
        Point-of-care ultrasound in the neonatal intensive care unit: international perspectives.
        Semin Fetal Neonatal Med. 2011; 16: 61-68
        • Coker B.J.
        • Zimmerman J.M.
        Why anesthesiologists must incorporate focused cardiac ultrasound into daily practice.
        Anesth Analg. 2017; 124: 761-765
        • Bhagra A.
        • Tierney D.M.
        • Sekiguchi H.
        • Soni N.J.
        Point-of-care ultrasonography for primary care physicians and general internists.
        Mayo Clin Proc. 2016; 91: 1811-1827
        • Shah S.P.
        • Shah S.P.
        • Fils-Aime R.
        • et al.
        Focused cardiopulmonary ultrasound for assessment of dyspnea in a resource-limited setting.
        Crit Ultrasound J. 2016; 8: 7
        • Gharahbaghian L.
        • Anderson K.L.
        • Lobo V.
        • Huang R.W.
        • Poffenberger C.M.
        • Nguyen P.D.
        Point-of-care ultrasound in austere environments: a complete review of its utilization, pitfalls, and technique for common applications in austere settings.
        Emerg Med Clin North Am. 2017; 35: 409-441
        • Yates J.G.
        • Baylous D.
        Aeromedical ultrasound: the evaluation of point-of-care ultrasound during helicopter transport.
        Air Med J. 2017; 36: 110-115
        • Larson D.B.
        • Johnson L.W.
        • Schnell B.M.
        • Salisbury S.R.
        • Forman H.P.
        National trends in CT use in the emergency department: 1995-2007.
        Radiology. 2011; 258: 164-173
        • Tang N.
        • Stein J.
        • Hsia R.Y.
        • Maselli J.H.
        • Gonzales R.
        Trends and characteristics of US emergency department visits, 1997–2007.
        JAMA. 2010; 304: 664-670
        • Levin D.C.
        • Rao V.M.
        • Parker L.
        • Frangos A.J.
        Continued growth in emergency department imaging is bucking the overall trends.
        J Am Coll Radiol. 2014; 11: 1044-1047
        • Rosenkrantz A.B.
        • Hanna T.N.
        • Babb J.S.
        • Duszak Jr., R.
        Changes in emergency department imaging: perspectives from national patient surveys over two Decades.
        J Am Coll Radiol. 2017; 14: 1282-1290
        • Korley F.K.
        • Pham J.C.
        • Kirsch T.D.
        Use of advanced radiology during visits to US emergency departments for injury-related conditions, 1998-2007.
        JAMA. 2010; 304: 1465-1471
        • Tong G.E.
        • Staudenmayer K.
        • Lin F.
        • Hsia R.Y.
        Use of emergency department imaging in patients with minor trauma.
        J Surg Res. 2016; 203: 238-245
        • Brink J.A.
        • Amis Jr., E.S.
        Image wisely: a campaign to increase awareness about adult radiation protection.
        Radiology. 2010; 257: 601-602
        • Goske M.J.
        • Applegate K.E.
        • Boylan J.
        • et al.
        The image gently campaign: working together to change practice.
        AJR Am J Roentgenol. 2008; 190: 273-274
        • Shah P.M.
        Contrast echocardiography-a historical perspective.
        in: Nanda N.C. Schlief R. Advances in echo imaging using contrast enhancement. 1st ed. Springer, Netherlands1993: 3-8
        • Gramiak R.
        • Shah P.M.
        Echocardiography of the aortic root.
        Invest Radiol. 1968; 3: 356-366
        • Bou Chebl R.
        • Kiblawi S.
        • El Khuri C.
        • et al.
        Use of contrast-enhanced ultrasound for confirmation of central venous catheter placement: systematic review and meta-analysis.
        J Ultrasound Med. 2017; 36: 2503-2510
        • Marriott K.
        • Manins V.
        • Forshaw A.
        • Wright J.
        • Pascoe R.
        Detection of right-to-left atrial communication using agitated saline contrast imaging: experience with 1162 patients and recommendations for echocardiography.
        J Am Soc Echocardiogr. 2013; 26: 96-102
        • Calliada F.
        • Campani R.
        • Bottinelli O.
        • Bozzini A.
        • Sommaruga M.G.
        Ultrasound contrast agents: basic principles.
        Eur J Radiol. 1998; 27: S157-160
        • Lindner J.R.
        Microbubbles in medical imaging: current applications and future directions.
        Nat Rev Drug Discov. 2004; 3: 527-532
        • Kitzman D.W.
        • Goldman M.E.
        • Gillam L.D.
        • Cohen J.L.
        • Aurigemma G.P.
        • Gottdiener J.S.
        Efficacy and safety of the novel ultrasound contrast agent perflutren (definity) in patients with suboptimal baseline left ventricular echocardiographic images.
        Am J Cardiol. 2000; 86: 669-674
        • Keller M.W.
        • Segal S.S.
        • Kaul S.
        • Duling B.
        The behavior of sonicated albumin microbubbles within the microcirculation: a basis for their use during myocardial contrast echocardiography.
        Circ Res. 1989; 65: 458-467
        • Lusic H.
        • Grinstaff M.W.
        X-ray-computed tomography contrast agents.
        Chem Rev. 2013; 113: 1641-1666
        • Morel D.R.
        • Schwieger I.
        • Hohn L.
        • et al.
        Human pharmacokinetics and safety evaluation of SonoVue, a new contrast agent for ultrasound imaging.
        Invest Radiol. 2000; 35: 80-85
        • Quaia E.
        Microbubble ultrasound contrast agents: an update.
        Eur Radiol. 2007; 17: 1995-2008
        • Delorme S.
        • Krix M.
        Contrast-enhanced ultrasound for examining tumor biology.
        Cancer Imaging. 2006; 6: 148-152
        • Wei K.
        • Jayaweera A.R.
        • Firoozan S.
        • Linka A.
        • Skyba D.M.
        • Kaul S.
        Quantification of myocardial blood flow with ultrasound-induced destruction of microbubbles administered as a constant venous infusion.
        Circulation. 1998; 97: 473-483
        • Blaivas M.
        • Lyon M.
        • Brannam L.
        • Schwartz R.
        • Duggal S.
        Feasibility of FAST examination performance with ultrasound contrast.
        J Emerg Med. 2005; 29: 307-311
        • Calabrese E.
        • Catalano O.
        • Nunziata A.
        • D'Errico A.
        • Petrillo A.
        Bedside contrast-enhanced sonography of critically ill patients.
        J Ultrasound Med. 2014; 33: 1685-1693
        • ter Haar G.
        Safety and bio-effects of ultrasound contrast agents.
        Med Biol Eng Comput. 2009; 47: 893-900
        • Claudon M.
        • Cosgrove D.
        • Albrecht T.
        • et al.
        Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) - update 2008.
        Ultraschall Med. 2008; 29: 28-44
        • Barrett J.F.
        • Keat N.
        Artifacts in CT: recognition and avoidance.
        Radiographics. 2004; 24: 1679-1691
        • Omar A.
        • Freeman S.
        Contrast-enhanced ultrasound of the spleen.
        Ultrasound. 2016; 24: 41-49
        • Sodickson A.
        • Baeyens P.F.
        • Andriole K.P.
        • et al.
        Recurrent CT, cumulative radiation exposure, and associated radiation-induced cancer risks from CT of adults.
        Radiology. 2009; 251: 175-184
        • Brenner D.J.
        • Hall E.J.
        Computed tomography—an increasing source of radiation exposure.
        N Engl J Med. 2007; 357: 2277-2284
        • Miglioretti D.L.
        • Johnson E.
        • Williams A.
        • et al.
        The use of computed tomography in pediatrics and the associated radiation exposure and estimated cancer risk.
        JAMA Pediatr. 2013; 167: 700-707
        • Cokkinos D.
        • Antypa E.
        • Stefanidis K.
        • et al.
        Contrast-enhanced ultrasound for imaging blunt abdominal trauma - indications, description of the technique and imaging review.
        Ultraschall Med. 2012; 33: 60-67
        • Cosgrove D.
        Ultrasound contrast agents: an overview.
        Eur J Radiol. 2006; 60: 324-330
        • Thorelius L.
        Contrast-enhanced ultrasound in trauma.
        Eur Radiol. 2004; 14: P43-52
        • Bauer A.
        • Solbiati L.
        • Weissman N.
        Ultrasound imaging with SonoVue: low mechanical index real-time imaging.
        Acad Radiol. 2002; 9: S282-284
        • Catalano O.
        • Cusati B.
        • Nunziata A.
        • Siani A.
        Active abdominal bleeding: contrast-enhanced sonography.
        Abdom Imaging. 2006; 31: 9-16
        • Piscaglia F.
        • Nolsoe C.
        • Dietrich C.F.
        • et al.
        The EFSUMB guidelines and recommendations on the clinical practice of contrast enhanced ultrasound (CEUS): update 2011 on non-hepatic applications.
        Ultraschall Med. 2012; 33: 33-59
        • Barr R.G.
        How to develop a contrast-enhanced ultrasound program.
        J Ultrasound Med. 2017; 36: 1225-1240
        • Cagini L.
        • Gravante S.
        • Malaspina C.M.
        • et al.
        Contrast enhanced ultrasound (CEUS) in blunt abdominal trauma.
        Crit Ultrasound J. 2013; 5: S9
        • Muskula P.R.
        • Main M.L.
        Safety with echocardiographic contrast agents.
        Circ Cardiovasc Imaging. 2017; 10
        • Pinto F.
        • Valentino M.
        • Romanini L.
        • Basilico R.
        • Miele V.
        The role of CEUS in the assessment of haemodynamically stable patients with blunt abdominal trauma.
        Radiol Med. 2015; 120: 3-11
        • Darge K.
        • Papadopoulou F.
        • Ntoulia A.
        • et al.
        Safety of contrast-enhanced ultrasound in children for non-cardiac applications: a review by the society for pediatric radiology (SPR) and the international contrast ultrasound society (ICUS).
        Pediatr Radiol. 2013; 43: 1063-1073
        • Piskunowicz M.
        • Kosiak W.
        • Batko T.
        • Piankowski A.
        • Polczynska K.
        • Adamkiewicz-Drozynska E.
        Safety of intravenous application of second-generation ultrasound contrast agent in children: prospective analysis.
        Ultrasound Med Biol. 2015; 41: 1095-1099
        • Piscaglia F.
        • Bolondi L.
        Italian society for ultrasound in M, biology study group on ultrasound contrast a. The safety of Sonovue in abdominal applications: retrospective analysis of 23188 investigations.
        Ultrasound Med Biol. 2006; 32: 1369-1375
        • Wei K.
        • Mulvagh S.L.
        • Carson L.
        • et al.
        The safety of deFinity and Optison for ultrasound image enhancement: a retrospective analysis of 78,383 administered contrast doses.
        J Am Soc Echocardiogr. 2008; 21: 1202-1206
        • Tang C.
        • Fang K.
        • Guo Y.
        • et al.
        Safety of sulfur hexafluoride microbubbles in sonography of abdominal and superficial organs: retrospective analysis of 30,222 cases.
        J Ultrasound Med. 2017; 36: 531-538
        • Media ACoDaC
        ACR manual on contrast media.
        American College of Radiology, 2015
        • Bokor D.
        • Chambers J.B.
        • Rees P.J.
        • Mant T.G.
        • Luzzani F.
        • Spinazzi A.
        Clinical safety of SonoVue, a new contrast agent for ultrasound imaging, in healthy volunteers and in patients with chronic obstructive pulmonary disease.
        Invest Radiol. 2001; 36: 104-109
        • Reilly J.P.
        • Tunick P.A.
        • Timmermans R.J.
        • Stein B.
        • Rosenzweig B.P.
        • Kronzon I.
        Contrast echocardiography clarifies uninterpretable wall motion in intensive care unit patients.
        J Am Coll Cardiol. 2000; 35: 485-490
        • Kurt M.
        • Shaikh K.A.
        • Peterson L.
        • et al.
        Impact of contrast echocardiography on evaluation of ventricular function and clinical management in a large prospective cohort.
        J Am Coll Cardiol. 2009; 53: 802-810
        • Tong K.L.
        • Kaul S.
        • Wang X.Q.
        • et al.
        Myocardial contrast echocardiography versus thrombolysis in myocardial infarction score in patients presenting to the emergency department with chest pain and a nondiagnostic electrocardiogram.
        J Am Coll Cardiol. 2005; 46: 920-927
        • Rinkevich D.
        • Kaul S.
        • Wang X.Q.
        • et al.
        Regional left ventricular perfusion and function in patients presenting to the emergency department with chest pain and no ST-segment elevation.
        Eur Heart J. 2005; 26: 1606-1611
        • Catalano O.
        • Aiani L.
        • Barozzi L.
        • et al.
        CEUS in abdominal trauma: multi-center study.
        Abdom Imaging. 2009; 34: 225-234
        • Valentino M.
        • Ansaloni L.
        • Catena F.
        • Pavlica P.
        • Pinna A.D.
        • Barozzi L.
        Contrast-enhanced ultrasonography in blunt abdominal trauma: considerations after 5 years of experience.
        Radiol Med. 2009; 114: 1080-1093
        • Sawhney S.
        • Wilson S.R.
        Can ultrasound with contrast enhancement replace nonenhanced computed tomography scans in patients with contraindication to computed tomography contrast agents?.
        Ultrasound Q. 2017; 33: 125-132
        • Valentino M.
        • Serra C.
        • Pavlica P.
        • Barozzi L.
        Contrast-enhanced ultrasound for blunt abdominal trauma.
        Semin Ultrasound CT MR. 2007; 28: 130-140
        • Cokkinos D.D.
        • Antypa E.
        • Kalogeropoulos I.
        • et al.
        Contrast-enhanced ultrasound performed under urgent conditions. Indications, review of the technique, clinical examples and limitations.
        Insights Imaging. 2013; 4: 185-198
        • Pinto F.
        • Miele V.
        • Scaglione M.
        • Pinto A.
        The use of contrast-enhanced ultrasound in blunt abdominal trauma: advantages and limitations.
        Acta Radiol. 2014; 55: 776-784
        • D'Onofrio M.
        • Crosara S.
        • De Robertis R.
        • Canestrini S.
        • Mucelli R.P.
        Contrast-enhanced ultrasound of focal liver lesions.
        AJR Am J Roentgenol. 2015; 205: W56-66
        • Gorg C.
        The forgotten organ: contrast enhanced sonography of the spleen.
        Eur J Radiol. 2007; 64: 189-201
        • Valentino M.
        • Serra C.
        • Zironi G.
        • De Luca C.
        • Pavlica P.
        • Barozzi L.
        Blunt abdominal trauma: emergency contrast-enhanced sonography for detection of solid organ injuries.
        AJR Am J Roentgenol. 2006; 186: 1361-1367
        • Sessa B.
        • Trinci M.
        • Ianniello S.
        • Menichini G.
        • Galluzzo M.
        • Miele V.
        Blunt abdominal trauma: role of contrast-enhanced ultrasound (CEUS) in the detection and staging of abdominal traumatic lesions compared to US and CE-MDCT.
        Radiol Med. 2015; 120: 180-189
        • Lv F.
        • Tang J.
        • Luo Y.
        • et al.
        Emergency contrast-enhanced ultrasonography for pancreatic injuries in blunt abdominal trauma.
        Radiol Med. 2014; 119: 920-927
        • Lv F.
        • Tang J.
        • Luo Y.
        • et al.
        Contrast-enhanced ultrasound imaging of active bleeding associated with hepatic and splenic trauma.
        Radiol Med. 2011; 116: 1076-1082
        • Lv F.
        • Ning Y.
        • Zhou X.
        • et al.
        Effectiveness of contrast-enhanced ultrasound in the classification and emergency management of abdominal trauma.
        Eur Radiol. 2014; 24: 2640-2648
        • Holmes J.F.
        • Kelley K.M.
        • Wootton-Gorges S.L.
        • et al.
        Effect of abdominal ultrasound on clinical care, outcomes, and resource use among children with blunt torso trauma: a randomized clinical trial.
        JAMA. 2017; 317: 2290-2296
        • Armstrong L.B.
        • Mooney D.P.
        • Paltiel H.
        • et al.
        Contrast enhanced ultrasound for the evaluation of blunt pediatric abdominal trauma.
        J Pediatr Surg. 2018; 53: 548-552
        • Menichini G.
        • Sessa B.
        • Trinci M.
        • Galluzzo M.
        • Miele V.
        Accuracy of contrast-enhanced ultrasound (CEUS) in the identification and characterization of traumatic solid organ lesions in children: a retrospective comparison with baseline US and CE-MDCT.
        Radiol Med. 2015; 120: 989-1001
        • Valentino M.
        • Serra C.
        • Pavlica P.
        • et al.
        Blunt abdominal trauma: diagnostic performance of contrast-enhanced US in children—initial experience.
        Radiology. 2008; 246: 903-909
        • Mihalik J.E.
        • Smith R.S.
        • Toevs C.C.
        • Putnam A.T.
        • Foster J.E.
        The use of contrast-enhanced ultrasound for the evaluation of solid abdominal organ injury in patients with blunt abdominal trauma.
        J Trauma Acute Care Surg. 2012; 73: 1100-1105
        • Catalano O.
        • Lobianco R.
        • Cusati B.
        • Siani A.
        Contrast-enhanced sonography for diagnosis of ruptured abdominal aortic aneurysm.
        AJR Am J Roentgenol. 2005; 184: 423-427
        • Goodacre S.
        • Sampson F.
        • Stevenson M.
        • et al.
        Measurement of the clinical and cost-effectiveness of non-invasive diagnostic testing strategies for deep vein thrombosis.
        Health Technol. Assess. 2006; 10 (iii-iv): 1-168
        • Smith A.
        • Parker P.
        • Byass O.
        • Chiu K.
        Contrast sonovenography - is this the answer to complex deep vein thrombosis imaging?.
        Ultrasound. 2016; 24: 17-22
        • Yan J.P.
        • Li W.Q.
        • Wang Z.F.
        • Guo B.L.
        Application of contrast-enhanced ultrasound before inferior vena cava filter recovery.
        Int Angiol. 2017; 36: 474-481
        • Linde H.N.
        • Holland A.
        • Greene B.H.
        • Gorg C.
        Contrast-enhancend sonography (CEUS) in pneumonia: typical patterns and clinical value - a retrospective study on n = 50 patients.
        Ultraschall Med. 2012; 33: 146-151
        • Bartelt S.
        • Trenker C.
        • Gorg C.
        • Neesse A.
        Contrast-enhanced ultrasound of embolic consolidations in patients with pulmonary embolism: a pilot study.
        J Clin Ultrasound. 2016; 44: 129-135
        • Trenker C.
        • Apitzsch J.C.
        • Pastor S.
        • Bartelt S.
        • Neesse A.
        • Goerg C.
        Detection of peripheral embolic consolidations using contrast-enhanced ultrasonography in patients with no evidence of pulmonary embolism on computed tomography: a pilot study.
        J Clin Ultrasound. 2017; 45: 575-579
        • Kummer T.
        • Hartman T.M.
        • White J.L.
        Diagnosis of an actively bleeding rectus sheath hematoma by contrast-enhanced ultrasound.
        Med Ultrason. 2017; 19: 239-240
        • Xu H.X.
        Contrast-enhanced ultrasound: the evolving applications.
        World J Radiol. 2009; 1: 15-24
        • Chung Y.E.
        • Kim K.W.
        Contrast-enhanced ultrasonography: advance and current status in abdominal imaging.
        Ultrasonography. 2015; 34: 3-18
        • Schneider A.
        • Johnson L.
        • Goodwin M.
        • Schelleman A.
        • Bellomo R.
        Bench-to-bedside review: contrast enhanced ultrasonography—a promising technique to assess renal perfusion in the ICU.
        Crit Care. 2011; 15: 157
        • Duerschmied D.
        • Olson L.
        • Olschewski M.
        • et al.
        Contrast ultrasound perfusion imaging of lower extremities in peripheral arterial disease: a novel diagnostic method.
        Eur Heart J. 2006; 27: 310-315